Association between brain N-acetylaspartate levels and sensory and motor dysfunction in patients who have spinal cord injury with spasticity:an observational case-control study

Spinal cord injury is a severe and devastating disease,and spasticity is a common and severe complication that is notoriously refractory to treatment.However,the pathophysiological mechanisms underlying spasticity and its development remain largely unknown.The goal of the present study was to find differences,if any,in metabolites of the left precentral gyrus and basal ganglia of patients who have spinal cord injury with or without spasticity,and to explore the relationship between the brain metabolite concentrations and clinical status.Thirty-six participants were recruited for magnetic resonance spectroscopic examination:23 with spinal cord injury(12 with spasticity and 11 without spasticity)and 13 healthy controls.We acquired localized proton spectra from the precentral gyrus and basal ganglia via 10 mm^(3) voxels.Notably,univariate linear regression analysis demonstrated that the lower that the N-acetylaspartate concentration(a marker for neuronal loss)was in the precentral gyrus of the patients,the lower their ASIA(American Spinal Injury Association)light-touch scores,pinprick scores,and motor scores.Additionally,longer durations of injury were associated with higher N-acetylaspartate levels in the precentral gyrus.Compared with the healthy participants and patients without spasticity,N-acetylaspartate levels in the patients with spasticity were significantly lower in both the precentral gyrus and basal ganglia.Lower N-acetylaspartate levels also correlated with greater sensory and motor dysfunction in the patients who had spinal cord injury with spasticity.

Extracorporeal shock wave for plantar flexor spasticity in spinal cord injury:A case report and review of literature

BACKGROUND Approximately 65%-78%of patients with a spinal cord injury(SCI)develop any symptom of spasticity.The aim of this study was to investigate the tolerability and short-term effects of radial extracorporeal shock wave therapy(r ESWT)on plantar flexor spasticity in a patient with incomplete SCI.CASE SUMMARY An 18-year-old man with an incomplete SCI completed five sessions of r ESWT.The primary outcomes were the changes in ankle-passive range of motion(APROM)and passive resistive force to ankle dorsiflexion.The outcomes were assessed at baseline(T0),immediately after treatment(T1)and 1 wk after the end of treatment(T2).The A-PROM increased by 15 degrees at T1 and 25 degrees at T2 compared with T0.The passive resistive force to ankle dorsiflexion at low velocity decreased by 33%at T1 and 55%at T2 in the gastrocnemius muscle and by 41%at T1 and 39%at T2 in the soleus muscle compared with T0.At high velocity,it also decreased by 44%at T1 and 30%at T2 in the gastrocnemius muscle compared with T0.However,in the soleus muscle,the change was minor,with a decrease of 12%at T1 and increased by 39%at T2 compared with T0.CONCLUSION In this patient,the findings showed that r ESWT combined with conventional therapy was well-tolerated and could be effective in improving A-PROM and passive resistive force to ankle dorsiflexion in the short-term.Further randomized controlled clinical trials with longer period of follow-up are necessary to confirm the results obtained in patients with SCI.

Expression of DRD1 mRNA after Spinal Cord Injury Induced Spasticity in Rats

[Objectives]To investigate the spasticity of rat tail and the expression of dopamine receptor-1(DRD1)mRNA in the spinal cord after spinal cord injury(SCI)induced tail spasticity in rats.[Methods]Adult male Wistar rats were randomly divided into Sham group and SCI group.The second sacral spinal cord(S2)segment of SCI rats was completely transected.60 d after operation,the rat tail spasticity was scored,and then the spinal cord tissues below the level of S2 spinal cord transection were taken.The expression of DRD1 mRNA in the sacrococcygeal spinal cord was detected by qPCR.In addition,3 normal rats were used for DAR/neuronal nuclei(NeuN)and DRD1/choline acetyltransferase(ChAT)immunofluorescence staining to study the distribution of DRD1 in spinal cord and the properties of DRD1 positive cells.[Results]60 d after operation in SCI group,the tail spasticity of rats developed fully,and the symptoms of spasticity were typical.qPCR results showed that the expression of DRD1 mRNA in SCI group was significantly lower than that in Sham group(P<0.05).DRD1 was widely distributed in the dorsal horn,intermediate zone and ventral horn at the sacrococcygeal end of the rat spinal cord.[Conclusions]The decrease of DRD1 mRNA expression after SCI may be related to the occurrence and development of spasticity.

Effects of High Frequency Repetitive Transcranial Magnetic Stimulation on KCC2 Expression in Rats with Spasticity Following Spinal Cord Injury

The effect of high-frequency repetitive transcranial magnetic stimulation（r TMS） on potassium-chloride cotransporter-2（KCC2） protein expression following spinal cord injury（SCI） and the action mechanism were investigated. SCI models were established in SD rats. Five groups were set up randomly： normal control group, SCI 7-day（7 D） model group, SCI 14-day（14 D） model group, SCI-7 DrTMS group and SCI-14 DrTMS group（n=5 each）. The rats in SCI rTMS groups were treated with 10 Hz rTMS from 8 th day and 15 th day after SCI respectively, once every day, 5 days every week, a total of 4 weeks. After the model establishment, motor recovery and spasticity alleviation were evaluated with BBB scale once a week till the end of treatment. Finally, different parts of tissues were dissected out for detection of variations of KCC2 protein using Western blotting and polymerase chain reaction（PCR） technique. The results showed that the BBS scores after treatment were significantly higher in SCI-7 DrTMS group than in SCI-14 DrTMS group（P〈0.05）. As compared with normal control groups, The KCC2 protein in SCI model groups was down-regulated after SCI, and the decrease was much more significant in SCI-14 D model group than in SCI-7 D group（P〈0.05）. As compared with SCI model groups, KCC2 protein in rTMS groups was up-regulated after the treatment（P〈0.05）. The up-regulation of KCC2 protein content and expression was more obvious in SCI-7 DrTMS group than in SCI-14 DrTMS group（P〈0.05）. It was concluded that 10 Hz rTMS can alleviate spasticity in rats with SCI, which might be attributed to the up-regulation of KCC2 protein. It was also suggested that the high-frequency rTMS treatment after SCI at early stage might achieve more satisfactory curative effectiveness.

Reduction of epinephrine in the lumbar spinal cord following repetitive blast-induced traumatic brain injury in rats

Traumatic brain inju ry-induced unfavorable outcomes in human patients have independently been associated with dysregulated levels of monoamines,especially epinephrine,although few preclinical studies have examined the epinephrine level in the central nervous system after traumatic brain injury.Epinephrine has been shown to regulate the activities of spinal motoneurons as well as increase the heart rate,blood pressure,and blood flow to the hindlimb muscles.Therefore,the purpose of the present study was to determine the impact of repeated blast-induced traumatic brain injury on the epinephrine levels in seve ral function-s pecific central nervous system regions in rats.Following three repeated blast injuries at 3-day intervals,the hippocampus,motor cortex,locus coeruleus,vestibular nuclei,and lumbar spinal cord were harvested at post-injury day eight and processed for epinephrine assays using a high-sensitive electrochemical detector cou pled with high-performance liquid chromatography.Our results showed that the epinephrine levels were significantly decreased in the lumbar spinal cord tissues of blast-induced traumatic brain injury animals compared to the levels detected in age-and sex-matched sham controls.In other function-specific central nervous system regions,although the epinephrine levels were slightly altered following blast-induced tra u matic brain injury,they were not statistically significant.These results suggest that blast injury-induced significant downregulation of epinephrine in the lumbar spinal cord could negatively impact the motor and cardiovascular function.This is the first repo rt to show altered epinephrine levels in the spinal cord following repetitive mild blast-induced traumatic brain injury.

Non-invasive brain stimulation to promote motor and functional recovery following spinal cord injury

We conducted a systematic review of studies using non-invasive brain stimulation（NIBS： repetitive transcranial magnetic stimulation（r TMS） and transcranial direct current stimulation（t DCS）） as a research and clinical tool aimed at improving motor and functional recovery or spasticity in patients following spinal cord injury（SCI） under the assumption that if the residual corticospinal circuits could be stimulated appropriately, the changes might be accompanied by functional recovery or an improvement in spasticity. This review summarizes the literature on the changes induced by NIBS in the motor and functional recovery and spasticity control of the upper and lower extremities following SCI.

Skeletal muscle stiffness as measured by magnetic resonance elastography after chronic spinal cord injury:a cross-sectional pilot study

Skeletal muscle stiffness is altered after spinal cord injury(SCI).Assessing muscle stiffness is essential for rehabilitation and pharmaceutical interventions design after SCI.The study used magnetic resonance elastography to assess the changes in stiffness after chronic SCI compared to matched able-bodied controls and determine its association with muscle size,spasticity,and peak torque in persons with SCI.Previous studies examined the association between muscle stiffness and spasticity,however,we are unaware of other studies that examined the effects of muscle composition on stiffness after SCI.Ten participants(one female)with chronic SCI and eight(one female)matched able-bodied controls participated in this cross-sectional study.Magnetic resonance elastography was utilized to monitor stiffness derived from shear waves propagation.Modified Ashworth scale was used to evaluate spasticity scores in a blinded fashion.Peak isometric and isokinetic torques were measured using a biodex dynamometer.Stiffness values were non-significantly lower(12.5%;P=0.3)in the SCI group compared to able-bodied controls.Moreover,stiffness was positively related to vastus lateralis whole muscle cross-sectional area(CSA)(r2=0.64,P<0.005)and vastus lateralis absolute muscle CSA after accounting for intramuscular fat(r2=0.78,P<0.0007).Stiffness was also positively correlated to both isometric(r2=0.55-0.57,P<0.05)and isokinetic peak(r2=0.46-0.48,P<0.05)torques.Our results suggest that larger clinical trial is warranted to confirm the preliminary findings that muscle stiffness is altered after SCI compared to healthy controls.Stiffness appeared to be influenced by infiltration of intramuscular fat and modestly by the spasticity of the paralyzed muscles.The preliminary data indicated that the relationship between muscle stiffness and peak torque is not altered with changing the frequency of pulses or angular velocities.All study procedures were approved by the Institutional Review Board at the Hunter Holmes McGuire VA Medical Center,USA(IRB#:02314)on May 3,2017.

Long-term effect of intrathecal baclofen treatment on bone health and body composition after spinal cord injury:A case matched report

BACKGROUND Severe spasticity may negatively impact functionality and quality of life after spinal cord injury(SCI).Intrathecal baclofen treatment(IBT)is effectively used to manage severe spasticity and reduce comorbidities.However,long-term IBT may have a negative effect on bone mineral content(BMC),bone mineral density(BMD)and body composition(such as percentage fat mass and lean body mass).We demonstrated the negative effects of long-term IBT use in a single case compared with two non-IBT users.CASE SUMMARY A 46-year old Caucasian male Veteran(case)with a 21 year history of complete tetraplegia(complete C6 SCI)was implanted with IBT for 20 years.The case was matched to two participants with different time since injuries[2(match 1)and 13(match 2)years]without IBT.Knee BMC and BMD at the epiphysis and metaphysis of the distal femur and proximal tibia were evaluated using dual knee and the dual femur modules of GE Lunar iDXA software.Total and leg body composition assessments were also conducted for the three participants.Potential effect of long-term IBT was demonstrated by changes in BMD,consistent with bone demineralization,at the distal femur and proximal tibia and changes in percentage fat mass and lean mass of legs.The case showed 113%lower BMD at the distal femur,and 78.1%lower at the proximal tibia compared to match 1,moreover the case showed 45%lower BMD at the distal femur,and no observed changes at the proximal tibia compared to match 2.The case had 27.1%and 16.5%greater leg%fat mass compared to match 1 and match 2,respectively.Furthermore,the case had 17.4%and 11.8%lower%leg lean mass compared to match 1 and match 2,respectively.CONCLUSION Long-term IBT may impact bone health and body composition parameters in persons with complete SCI.It may be prudent to encourage regular screening of individuals on long-term IBT considering the prevalence of osteoporosis related fractures,cardiovascular diseases,and metabolic disorders in this population.

重复经颅磁刺激联合冲击波治疗脊髓损伤后痉挛患者的疗效观察

目的:观察重复经颅磁刺激(rTMS)联合冲击波(ESWT)对脊髓损伤(SCI)后痉挛患者状态的疗效。方法:选取2020年1月-2022年12月新余市人民医院收治的45例不完全性SCI伴有下肢痉挛患者作为研究对象,随机将其分为A组、B组、C组,每组各15例。A组患者给予常规康复治疗,B组患者在A组的基础上给予rTMS治疗;C组患者在A组的基础上给予rTMS联合ESWT治疗。比较治疗前后分别对三组患者改良的Ashworth量表(MAS)、Fugl-Meyer评定量表(FMA)、改良Barthel指数(MBI)情况。结果:治疗后,三组患者MAS明显低于治疗前、FMA及MBI明显高于治疗前,差异有统计学意义(t=3.292、4.583、12.649、-8.921、-12.466、-24.234、-10.208、-13.256、-20.327,P<0.01),其中C组患者MAS均低于B组患者和A组患者,差异有统计学意义(t=2.168、7.341,P<0.05);C组患者FMA、MBI均高于B组患者和A组患者,差异有统计学意义(t=-2.568、-3.877、-2.244、-4.049,P<0.05)。结论:rTMS联合ESWT治疗可以有效改善SCI后患者下肢痉挛状态,同时可提高患者下肢运动功能及日常生活活动能力。

胸_(1)脊神经根切断治疗手痉挛性瘫痪的临床效果观察

目的探讨胸_(1)脊神经根切断治疗手痉挛性瘫痪的临床效果。方法回顾性分析2006年10月至2021年7月在北京积水潭医院接受胸_(1)脊神经根切断术治疗的7例手痉挛性瘫痪患者的临床资料。其中男4例,女3例;脑外伤5例,脑瘫2例;从脑外伤或脑瘫发病到手术的时间为1~18年,平均(6.7±5.9)年。所有患者均为单侧肢体受累,屈指肌肌张力3级6例、2级1例,屈指肌肌力4级4例、3级3例。观察术后患者屈指肌肌张力和肌力的恢复情况,以及手功能改良House上肢功能分级(House Functional Classification,HFC)的变化。结果所有患者手术顺利,术后随访6~36个月,平均(15.4±10.3)个月。7例患者末次随访时屈指肌肌张力均较术前降低2个等级且肌力无减弱,疗效评定均为优。术后早期屈指肌肌力均有明显降低,至末次随访时均恢复到术前水平。3例患者末次随访时手功能改良HFC分级由术前的2级增至5级或以上,恢复了手的主动抓握及日常使用功能。7例患者最终的手功能改良HFC分级由术前的(1.6±0.8)级提高到末次随访时的(4.0±1.7)级。术后第1天7例患者均有小指及前臂内侧感觉麻木,至末次随访时均恢复正常。结论胸_(1)脊神经根切断术治疗手屈指痉挛性瘫痪效果满意,值得临床应用。

脊髓损伤后痉挛相关基因的生物信息学分析

目的:对大鼠脊髓损伤(SCI)后痉挛相关基因进行生物信息学分析,探索SCI后痉挛发生的分子机制。方法:在GEO数据库下载SCI后痉挛的基因表达谱芯片数据GSE16710,采用在线工具GEO 2R筛选差异表达基因(DEG),筛选标准为P<0.05及|log2FC|≥1,通过火山图进行可视化;使用DAVID数据库对筛选的DEG进行GO功能富集和KEGG通路分析,使用ImageGP可视化;通过STRING数据库构建DEGs的蛋白-蛋白互作(PPI)网络分析,利用Cytoscape软件进行可视化,并运用CytoHubba插件和DEPs的degree值筛选PPI网络中前10位的关键基因。结果:总共筛选得到313个DEGs,其中有92个上调基因和221个下调基因;GO富集分析结果发现DEGs主要集中在谷氨酸能突触传递的调节、突触传递的正向调节、神经元投射发展的调节及磷脂酰肌醇-3激酶信号等生物学过程上;KEGG通路分析表明,DEGs主要富集在长时程增强、谷氨酸能突触、MAPK信号途径及cAMP信号途径等通路上;PPI分析发现,Mapt、Gad1、Gria2、Fmr1、Reln、Mbp及Cav1等前10位是关键基因。结论:通过生信工具分析了SCI后痉挛中的关键DEGs和通路,帮助理解其分子机制及在痉挛发生、发展过程中的作用,为该病的治疗提供了理论依据。

A型肉毒毒素治疗脊髓损伤痉挛状态的临床研究

目的 :研究A型肉毒毒素对脊髓损伤痉挛状态的治疗作用。方法 :选择 9例脊髓损伤痉挛状态患者的 76块对功能影响较大且改良Ashworth分级≥Ⅱ级的痉挛肌进行A型肉毒毒素多点注射 ,记录治疗前及治疗后 3天、1周、1个月、2个月、3个月痉挛肌改良Ashworth分级、痉挛性疼痛评分 (VAS)、夜间抽搐的频率、内收肌角、直腿抬高角及FIM运动分的变化。结果 :注射后 3天即有 72 .3 %靶肌的改良Ashworth分级下降 (P <0 .0 1 ) ,1个月时所有靶肌 (1 0 0 % )的改良Ashworth分级显著下降 (P <0 .0 1 ) ,60 %的靶肌疗效持续时间≥ 3个月。注射后痉挛性疼痛(VAS)、夜间抽搐的频率、内收肌角、直腿抬高角显著改善 (P <0 .0 1 ) ,FIM运动分注射 1个月后持续改善 (P <0 .0 1 )。结论 :A型肉毒毒素对脊髓损伤痉挛性疼痛、抽搐及痉挛性关节活动度障碍有明显疗效 。

联合用药治疗脊髓损伤中重度痉挛的临床观察

目的观察联合应用巴氯芬、替扎尼定和乙哌立松治疗脊髓损伤中重度痉挛患者的临床效果。方法住院脊髓损伤中重度痉挛患者18例,采用2种或3种药物联合应用,所有患者连续服药2个月,并随访4个月以上。采用改良Ashworth评分进行评定,同时观察痉挛缓解持续时间及血压、血尿常规和肝肾功能。结果重度痉挛患者16例中,3例改良Ashworth评分降低3级,12例降低2级,1例降低1级,伴神经痛明显减轻;2例中度痉挛患者均降低1级,伴神经痛明显减轻。服药后肝肾功能未见异常,出现轻度嗜睡2例。结论联合用药对脊髓损伤中重度痉挛患者的解痉效果明显,副作用小。

温泉水疗对改善胸段不完全性脊髓损伤患者肌痉挛的疗效观察

目的观察胸段不完全性脊髓损伤后肌痉挛患者经过温泉水疗结合康复治疗后的疗效。方法将25例胸段不完全性脊髓损伤后肌痉挛患者分为治疗组(15例)和对照组(10例),对照组应用常规康复疗法,治疗组在常规康复疗法基础上加温泉水疗。治疗前、后进行改良的Ashworth痉挛评分法(MAS)评定。结果两组患者治疗后MAS评分较治疗前有非常显著性差异(P<0.01),并且治疗组疗效优于对照组(P<0.05)。结论温泉水疗能有效改善胸段不完全性脊髓损伤后肌痉挛。

犬脊髓损伤痉挛性膀胱动物模型的建立及尿动力学分析

目的:探讨犬脊髓损伤后痉挛性膀胱模型的建立。方法:12只成熟雄性比格犬,在T10水平硬膜外夹闭脊髓,制作脊髓损伤模型。用尿动力学检测分析造模术前及术后每周的最大膀胱容量、膀胱压力、膀胱顺应性和尿道压力,直到模型成功。结果:12只犬死亡2只,其余10只造模成功,造模成功时尿动力学指标如下:与术前相比最大膀胱容量减少,膀胱顺应性下降,膀胱压力上升,其差异均有显著性意义(P<0.05);尿道压力与术前相比无显著性差异(P>0.05)。造模成功时间为2—5周,其中5只为2周,1只为3周,2只为4周,2只为5周。结论:犬痉挛性膀胱模型符合骶上脊髓损伤后的膀胱表现,适用于痉挛性膀胱的研究。

直肠电刺激缓解脊髓损伤后痉挛状态的机理

目的：研究直肠电刺激（ＲＰＥＳ）缓解脊髓损伤（ＳＣＩ）后痉挛状态的作用机理。方法：１０例ＳＣＩ后痉挛患者和１０例偏瘫后痉挛患者，在ＲＰＥＳ治疗和口服Ｂａｃｌｏｆｅｎ前后进行康复评分和电生理指标测定，包括Ｆ波，屈肌反射，Ｈ反射，Ｔ反射。结果：ＳＣＩ患者经ＲＰＥＳ治疗后，下肢康复评分显著降低（Ｐ＜０．００１），Ｆ波振幅、时程、Ｆ／Ｍ比显著降低（Ｐ＜０．０５），屈肌反射振幅、时程显著降低（Ｐ＜０．０１），Ｂａｃｌｏｆｅｎ治疗后，康复评分显著降低，Ｆ波振幅、时程、Ｆ／Ｍ比显著降低（Ｐ＜０．０５）。偏瘫患者患侧下肢康复评分和电生理指标均无显著变化。结论：ＲＰＥＳ对降低ＳＣＩ后痉挛状态有较好的疗效，主要作用部位在脊髓节段，作用机理与降低α运动神经元活性和一般中间神经元活性有关，而与γ运动神经元及Ｒｅｎｓｈａｗ细胞活性无关。其解痉作用可能部分与γ氨基丁酸相关，但仍有其它神经介质参与。

选择性骶神经前根切断术治疗脊髓损伤后痉挛性膀胱的初步报告

目的：研究治疗脊髓损伤后痉挛性膀胱的新手术方法。方法：利用骶神经根及骶丛神经相互间代偿的原理，设计了选择性骶神经前根切断术，治疗脊髓损伤后痉挛性膀胱。结果：术后患者膀胱痉挛明显缓解，膀胱贮尿及排尿功能得到明显改善，６个月后随访患者膀胱功能已达到或接近正常水平。结论：选择性骶神经前根切断术治疗脊髓损伤后痉挛性膀胱近期疗效显著。

A型肉毒素水电针腧穴注射治疗脊髓损伤后肌痉挛的临床研究

目的:探讨A型肉毒素(BTXA)水电针腧穴注射治疗脊髓损伤后肌痉挛的安全性及疗效。方法:2006年12月至2009年12月,收治脊髓损伤后出现肌痉挛的患者38例,男26例,女12例;年龄21～68岁,平均45.4岁。按入院时间随机分为3组,A组13例,采用BTXA水电针腧穴注射;B组13例,单纯注射BTXA;C组12例,单纯电针刺激。治疗后第6个月时对患者进行改良Ashworth(MAS)评分及临床痉挛指数CSI评分。结果:治疗后第6个月时38例患者获得随访,治疗前3组患者MAS评分分别为(3.10±0.14),(3.20±0.17),(3.10±0.16)分,CSI评分分别为(14.10±0.14),(14.30±0.11),(14.20±0.12)分,两项评分术前差异无统计学意义(P>0.05);治疗后第6个月时3组患者MAS评分分别为(1.10±0.16),(2.10±0.13),(2.00±0.14)分,CSI评分分别为(9.10±0.11),(12.10±0.14),(13.10±0.12)分,A组两项评分明显优于B、C组(P<0.05)。结论:中医水电针、腧穴与BTXA注射有机结合,互相弥补不足,能达到综合治疗的目的,可以安全、快速的减少肌痉挛患者的痛苦,提高生活质量,是治疗脊髓损伤后肌痉挛的全新、效佳的方法。

选择性骶神经根切断治疗脊髓损伤后痉挛性膀胱的实验研究

目的：观察选择性骶神经根切断治疗脊髓损伤痉挛性膀胱的实际疗效，探讨骶神经根高选择性切断的治疗机制及最佳手术方式。方法：雄性家犬１２ 只，制备成脊髓损伤后痉挛性膀胱模型，根据骶神经切断方式分为Ａ、Ｂ、Ｃ、Ｄ４ 组，通过尿流动力学检测及电生理观察，记录并计算骶神经切断前（ 对照组）及术后各组各项功能性指标的变化，并进行比较分析。结果：Ａ、Ｂ、Ｃ、Ｄ４ 组术后膀胱容量均明显高于术前对照组，尿道压力均低于术前对照组，其中Ｂ 组的膀胱贮尿功能、排空能力、尿道压力均接近正常，且对犬阴茎勃起功能无明显影响。结论：高选择性骶神经根切断治疗脊髓损伤后痉挛性膀胱有确实明显的疗效，是一种值得研究的新方法。

激活后抑制与痉挛的关系

近几年有研究发现,中枢神经系统损伤患者脊髓H反射激活后抑制的减少与痉挛严重程度相关性较高,可能对中枢神经系统损伤后痉挛的客观评价有潜在意义。本文介绍激活后抑制的概念、机制以及其影响因素。